Learning by Selection in the Trion Model of Cortical Organization

The basic issue of whether mammalian learning in cortex proceedsvia a selection principle, as stressed by Edelman, versus aninstructional one is of major importance. We present here arealization of selection learning in the trion model, whichis based on the Mountcastle columnar organizational principleof cortex. We suggest that mammalian cortex starts out withan a priori connectivity between minicolumns that is highlystructured in time and in space, competing between excitationand inhibition. This provides a "naive" repertoire of spatial-temporalfiring patterns that stimuli and internal pro-cessing map onto.These patterns can be learned with small modifications to theconnectivity strengths determined by a Hobbian learning rule.As various patterns are learned, the repertoire changes somewhatin order to respond property to various stimuli, but the majorityof all possible stimuli still map onto spatial-temporal firingpatterns of the original repertoire. In order to show that theexample presented here is showing true selectivity and is notan artifact of more stimuli evolving into the learned pattern,we develop a selectivity measure. We suggest that some formof instructional learning (in which connectivities are finelytuned) is present for difficult tasks requiring many trials,whereas very rapid learning involves selectional learning. Bothtypes of learning must be considered to understand behavior.     

Epidemiologic research using existing databases of environmental measures

When detailed information on individuals is not available, databases of environmental measures are sometimes used in epidemiologic studies to provide data on human exposure. The use of such databases is based on the assumption that the data are representative of individual human exposure and are applicable to the study. Twenty-six databases that contained data on the environment pertaining to California were summarized and evaluated by categorical criteria of spatial and temporal precision, availability, amount of quantitative information, "machine-readability," and type of environmental measure.     

Prediction of temperature rise in layered media from measured ultrasonic intensity data

It is now widely recognized that under some circumstances exposure to ultrasound at current diagnostic levels may result in undesirable heating in tissue. The National Council on Radiation Protection and Measurements (NCRP) and the American Institute of Ultrasound in Medicine (AIUM) in conjunction with the National Electrical Manufacturers Association (NEMA) have suggested relatively simple methods for estimating the in situ temperature rise based on simplified ultrasonic intensity profiles. In this paper, the measured spatial intensity distribution from three unscanned ultrasonic transducers is used in an integral solution to the bioheat equation to calculate the temperature increase in layered media, and these calculations are compared with the simple predictions under similar conditions. The transducers included weak and strong focusing devices and one device with a non-cylindrical beam. The ratio between the NCRP and AIUM/NEMA predictions varied from 0.5 to 2.3 in equivalent situations. The ratio between the simple predictions and the more detailed calculations varied from 0.7 to 3.2 for NCRP, and from 0.3 and 3.5 for AIUM/NEMA. These results highlight the need, firstly, to establish simple 'standard' methods for estimating likely temperature increase during clinical examination, and secondly to be clear about whether these methods are intended to give 'worst case' or 'typical' estimates.     

Nonhereditary p53 mutations in T-cell acute lymphoblastic leukemia are associated with the relapse phase

We have previously reported that greater than 60% of human leukemic T- cell lines possess mutations in the p53 tumor suppressor gene. To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations. Exons 4 through 9 and selected intron regions of the p53 gene were analyzed using polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. p53 mutations were found in 0 of 15 T-ALL diagnosis samples, as compared with 10 of 36 (28%) T-ALL relapse samples. To determine whether p53 mutations play a role in the recurrence (relapse) of T-ALL, two special groups of T-ALL patients were studied: (1) a group of 8 relapse patients whose disease was refractory to chemotherapeutic treatment, and (2) a group of 6 "paired" T-ALL cell samples from patients for whom we possess both diagnosis and relapse samples. Three of 8 relapsed patients (37.5%) whose disease was refractory to the reinduction of remission by chemotherapy possessed missense mutations of the p53 gene. All 3 cases had mutations in exon 5. Among the paired samples, 3 of 6 patients harbored p53 mutations at disease recurrence, but possessed only wild- type p53 alleles at diagnosis. One case had mutation on exon 4, 1 case in exon 5, and 1 case in exon 8 with loss of heterozygosity. These data clearly indicate that recurrence of T-ALL is associated with missense mutations in p53. Our results indicate that (1) mutations of p53 do occur in T-ALL in vivo, and such mutations are associated with the relapse phase of the disease; and (2) p53 mutation is involved in the progression of T-ALL. This conclusion is supported by our observation that the introduction of T-ALL-derived mutant p53 expression constructs into T-ALL cell lines further increases their growth rate in culture, enhances cell cloning in methylcellulose, and increases tumor formation in nude mice.     

Neurotoxicity of Radiosurgery

Radiosurgery is a technique to deliver (in most cases) a single fraction of ionizing radiation, usually in the range of 10 to 25 Gy, to a precisely localized intracranial volume of pathological tissue. The radiobiological principles that govern the practice of single-fraction radiosurgery differ from those of conventional fractionated external beam radiation therapy. Rather, the results are primarily a consequence of either vascular effects or antiproliferative effects. The neurotoxicity of radiosurgery can be described according to its time course (immediate, acute, or chronic) and severity (mild, moderate, severe, life-threatening, or fatal( based on existing definitions established by the Radiation Therapy Oncology Group. Current indications for radiosurgery include arteriovenous malformations, acoustic neuromas, brain metastases, high-grade and other gliomas, meningiomas, and pituitary adenomas. The efficacy of radiosurgery and the time course and severity of radiosurgical neurotoxicity are dependent both on the nature of the lesion being treated and the normal tissue milieu which the lesion resides. This article describes the spectrum of neurotoxicity reported in the medical literature pertaining to the current variety of space-occupying lesions, benign tumors, and malignant neoplasms for which radiosurgery currently is being used.     

Xanthogranulomatous pyelonephritis in childhood: Ultrasound and CT diagnosis

Four cases of diffuse xanthogranulomatous pyelonephritis (XPN) in young children are presented. In three patients the clinical picture was one of weight loss, anaemia and neutrophilia with a large renal mass. The fourth presented with haematuria. Ultrasound (US) and CT findings were almost identical in all four patients. US showed the affected kidney was massively enlarged but retained a reniform shape. Dilated fluid spaces containing calculi were present. CT confirmed the US findings and revealed peripheral enhancement without contrast excretion, with dilated calyceal spaces producing the bear paw sign. Extrarenal extension into abdominal wall and psoas muscle is typical and was well demonstrated by CT. The affected kidneys were non-functioning and nephrectomy was required. Typical US and CT features allow a confident diagnosis of XPN and appropriate early treatment.     

The effect of congenital anomalies on mortality risk in white and black infants.

OBJECTIVES: This population-based study examined the effect of all major congenital anomalies on the mortality of White and Black infants by infant sex, birthweight, gestational age, and lethality of the anomaly. The study also determined the total contribution of anomalies to infant mortality. METHODS: California Birth Defects Monitoring Program data were merged with linked birth-death files for 278,646 singleton non-Hispanic White and Black infants born in 1983 through 1986. Malformed infants were compared with nonmalformed infants to determine the effect of anomalies on mortality. RESULTS: The presence of any congenital anomaly increased mortality 9.0-fold (95% CI = 7.3, 11.1) for Black infants and 17.8-fold (95% CI = 16.2, 19.6) for White infants. Even "non-lethal" anomalies increased mortality up to 8.9-fold. Overall, anomalies contributed to 33% of White infant deaths, to 19% of Black infant deaths, and to over 60% of deaths among Black and White neonates weighing over 1499 g. CONCLUSIONS: The contribution of congenital anomalies to mortality of both low- (< 2500 g) and normal-birth-weight infants is substantially higher than previously estimated, representing a large public health problem for both Black and White infants.     

Medical issues relating to the Sydney Olympic Games

The Sydney Olympic Games in 2000 represent a significant medical and sporting challenge. Prior planning is the key to optimal performance, and team medical staff should be familiar with major medical and injury concerns of athletes and officials well prior to departure. A comprehensive team medical kit should be organised. Travel will be over great distances for many teams, so particular attention to optimising sleep and hydration is essential. The Olympic village experience can be overwhelming for some athletes, and medical staff should provide informed advice on food, transport and safety issues. Heat is less likely to be an issue than at recent summer Olympic Games, but should not be ignored completely. Major incidents can occur at any major sporting festival, and team medical staff should be appropriately prepared for these. All team medical staff should be aware of the current list of banned substances, and seek to minimise drug use by their athletes. After the event, an appropriate debriefing session should be held with a view to planning improvements for the future.